Chris Ormandy of Sydney's Garvan Institute of Medical Research said transcription factors were molecules that switched genes on or off. In this case, the transcription factor known as ELF5 inhibited sensitivity to estrogen very early in the life of a breast cancer cell.
In earlier research, Ormandy showed ELF5 was responsible for the development of the estrogen-receptor-negative cells in the breast during pregnancy that produce milk.
In the current study, Ormandy, Dr. Maria Kalyuga and Dr. David Gallego-Ortega showed the same molecular decision occurs in breast cancer and that ELF5 had the ability to change an existing tumor to an estrogen-insensitive type.
The team also described the genetic mechanisms by which ELF5 opposed the action of estrogen, and showed it was possible to alter the subtype of breast cancer by manipulating ELF5 levels.
"This work tells us that cancers which become refractory to anti-estrogen treatment often do so by elevating their levels of ELF5 and becoming functionally estrogen receptor negative," Ormandy said in a statement. "This raises the therapeutic option of manipulating ELF5 levels to treat breast cancer."
The findings were published online in the journal PLoS Biology.
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